This paper describes the synthesis of distillation sequences simultaneously with the synthesis of other process subsystems. An improved MINLP approach is proposed for the synthesis of complex problems. The improvements were made on three major MINLP levels. By postulating the superstructures we propose to use smaller and more compact superstructures of the distillation sequences included in the flowsheet superstructure rather than the usual tree and network representations. In the modelling step a higher degree of simultaneity has been accomplished by the use of simultaneous models of the distillation column and aggregated models of other process units. To facilitate the optimization phase the modified OA/ER algorithm [Kravanja and Grossmann, Ind. Engng. Chem. Res. 26, 1869-1880 (1994)], implemented in the computerized synthesizer PROSYN-MINLP, has been used to reduce the effect of nonconvexities. Also, a special initialization and linearization scheme for simultaneous synthesis of HEN has been proposed. The improved method is illustrated by the synthesis of the separation subsystem followed by the simultaneous synthesis of the heat integrated separation system and its heat exchanger network (HEN). Finally, the optimization of the overall process and the simultaneous synthesis of its distillation system and heat integrated HEN is presented.